Professor & patients' paper on the solvable biological challenge of ME/CFS: reader-friendly version
Simon McGrath provides a patient-friendly version of a peer-reviewed paper which highlights some of the most promising biomedical research on ME/CFS ...
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Circadian rhythms and redox state

Discussion in 'Other Health News and Research' started by kaffiend, Aug 28, 2012.

  1. kaffiend

    kaffiend Senior Member

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    California
    anne_likes_red and taniaaust1 like this.
  2. alex3619

    alex3619 Senior Member

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    Darn, I sometimes progress into something worse than non-24 hour circadian disorder. What does that say about my redox status? Bye, Alex

    PS This study (on the same site) shows how two proteins regulate fatty liver - the same proteins that are involved in circadian maintenance:

    http://www.sciencedaily.com/releases/2012/04/120406141753.htm
     
  3. kaffiend

    kaffiend Senior Member

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    I browsed a few other studies (in rats) that restored the redox state in the hypothalamus by injecting reduced glutathione into a nearby brain area filled with spinal fluid. I've long suspected that the hypothalamus is at the center of some ME/CFS cases.
     
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  4. MNC

    MNC Senior Member

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    Oh what a surprise. I have both fatty liver and non-24 circadian disorder.
     
  5. taniaaust1

    taniaaust1

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    I get 4 different sleep issues.. one being non 24 circadian disorder. Im so glad they are discovering new things in this area.
     
  6. alex3619

    alex3619 Senior Member

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    Tania, MNC, I see these problems more and more, particularly in longer term patients. The first few years with ME they are rare. By year 15 they are common. This is just an observation of a bunch of patients, but I think it might indicate a trend. Bye, Alex
     
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  7. taniaaust1

    taniaaust1

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    Its really hard to say,... I'll try to be more observant and see if I end up coming to the same conclusion as you have (thanks for sharing). I guess someone could do a poll for those who have sleep issues of the circardian kind, to find out how long people had ME/CFS before the circadian cycle went haywire. It would be interesting if your observation is correct. (progression of ME???)
     
  8. August59

    August59 Daughters High School Graduation

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    I'm at 8 years and I have had really bad circadian disorder. My bodies sleep cycle right now is got to sleep at 3am and sleep to 7am and might as well get up and try stretch some, then eat something and then look at a little news. Most of the time I try to go outside and just sit on the porch and get about 10 minutes of morning sun and fresh air. Change that a little, I have to feed the cats before I sit down on my chair on the porch. Go to the mail box and get the mail from the day before. By the time I usually read it my eyes have started crossing and it is 10am and I usually sleep till noon.

    Then I'm up until 3am the next morning. I had my 24 hour cortisol check about 4 months ago and it is just way off. It is below normal at 8am, 12pm it has risen to high normal and from there it is flatlined all the way through my 12am sample. Somewhere between 12am and 8am it falls from a high normal to below normal.

    I'm guessing that the cortisol starts falling after 12am with a steeper decline starting around 3am and that is why my sleep times wants to correlate. I'm geussing also that it starts it;s incline around 7am due to that being pretty much an automatic wake up for me, so I really wonder how low it is getting if it is already low at 8am.

    My intergrative doctor wants me to start a good adrenal extract in the am and take phosphadylserine(?) at about 9pm for awhile and see if we can get it to move toward more resemblence of a 24 hour circadian.

    He attributes it to 2 different things:
    1) Out of 4 sleep studies done over 8 - 9 years. I have never made it into the "Stag3 & Stage 4 - The Deep Sleep".
    *Minor exception was on 3rd sleep study I was taking a 7.5mg of Ambien and 6 grams of Xyrem (only once) and
    received 9 minutes of Stage 3 or Stage 4 sleep.
    2) The combination of CFS and Fibro and it's reported history of fragmenting sleep

    He is very concerned about me not getting any "Stage 3 or Stage 4 - Deep Sleep". The period that your in that sleep is like pulling intto the pits at a racing event and having to change all the tires, adjust wedge in threar and camber in the front, cleaning of the radiotor so engine will not run hot. The driver gets a few seconds to just relax his shoulders and arms, plus make any fine tuning ajustments on the engine if something is not running right.

    He said I'm probably getting some deep sleep on occasions, but at my age I should not be getting any less than 100 minutes a night of Stage 3 or Stage 4 sleep and it's obvious that I am not even getting close to that. And that there are not much if any options left if Xyrem is not putting me into deep sleep.
     
  9. richvank

    richvank Senior Member

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    Hi, all.

    The GD-MCB hypothesis has inferred low glutathione (and hence, oxidative stress) in the hypothalamus in ME/CFS since 2007, and this new work seems consistent with that.

    I inferred low glutathione in the hypothalamus to explain the low levels of the hormones normally secreted by the hypothalamus that have cysteine residues. Also, the hypothalamus does not have a rapid transsulfuration pathway, so would be expected not to be able to convert methionine to cysteine very well. In general, the organs and systems that have this limitation are the ones that are associated with symptoms in ME/CFS, and I have suggested that the reason is that they are among the first to go low in glutathione when there is a bodywide glutathione depletion.

    I note also that Dr. Shungu et al. have recently reported measuring glutathione depletion in another part of the brain in ME/CFS.

    All of this seems to continue to come together.

    Best regards,

    Rich
     
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  10. anne_likes_red

    anne_likes_red Senior Member

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    Hi Rich,
    I did a quick search but I couldn't find the recent Shungu study you mentioned. I'd like a link if you have it handy.
    Thanks in advance! :)
    Anne.
     
  11. richvank

    richvank Senior Member

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    Hi, Anne.

    Here's the abstract of Shungu's paper showing low glutathione in the brain in CFS:

    NMR Biomed. 2012 Sep;25(9):1073-87. doi: 10.1002/nbm.2772. Epub 2012 Jan 27.
    Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology.

    Shungu DC, Weiduschat N, Murrough JW, Mao X, Pillemer S, Dyke JP, Medow MS, Natelson BH, Stewart JM, Mathew SJ.
    Source

    Department of Radiology, Weill Medical College of Cornell University, New York, NY, USA.
    Abstract

    Chronic fatigue syndrome (CFS) is a complex illness, which is often misdiagnosed as a psychiatric illness. In two previous reports, using (1) H MRSI, we found significantly higher levels of ventricular cerebrospinal fluid (CSF) lactate in patients with CFS relative to those with generalized anxiety disorder and healthy volunteers (HV), but not relative to those with major depressive disorder (MDD). In this third independent cross-sectional neuroimaging study, we investigated a pathophysiological model which postulated that elevations of CSF lactate in patients with CFS might be caused by increased oxidative stress, cerebral hypoperfusion and/or secondary mitochondrial dysfunction. Fifteen patients with CFS, 15 with MDD and 13 HVs were studied using the following modalities: (i) (1) H MRSI to measure CSF lactate; (ii) single-voxel (1) H MRS to measure levels of cortical glutathione (GSH) as a marker of antioxidant capacity; (iii) arterial spin labeling (ASL) MRI to measure regional cerebral blood flow (rCBF); and (iv) (31) P MRSI to measure brain high-energy phosphates as objective indices of mitochondrial dysfunction. We found elevated ventricular lactate and decreased GSH in patients with CFS and MDD relative to HVs. GSH did not differ significantly between the two patient groups. In addition, we found lower rCBF in the left anterior cingulate cortex and the right lingual gyrus in patients with CFS relative to HVs, but rCBF did not differ between those with CFS and MDD. We found no differences between the three groups in terms of any high-energy phosphate metabolites. In exploratory correlation analyses, we found that levels of ventricular lactate and cortical GSH were inversely correlated, and significantly associated with several key indices of physical health and disability. Collectively, the results of this third independent study support a pathophysiological model of CFS in which increased oxidative stress may play a key role in CFS etiopathophysiology. Copyright © 2012 John Wiley & Sons, Ltd.
    Copyright © 2012 John Wiley & Sons, Ltd.
    PMID: 22281935
    Best regards,
    Rich
     
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  12. anne_likes_red

    anne_likes_red Senior Member

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    Thank you Rich :)
     

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